HP is an inappropriate immune response to inhaled antigens that causes: shortness of breath, a restrictive lung defect, interstitial infiltrates seen on lung imaging (CXR and high-resolution CT) caused by the accumulation of large numbers of activated T lymphocytes in the lungs. The disease is sometimes further characterized by episodic bouts of fever a few hours after exposure.
During the acute phase, respiratory symptoms (e.g. cough, dyspnea) are common but not universal, and chest imaging may be normal
Features of HP may vary based on the causative antigen
Pathophysiology unclear: immune complex-mediated (serum precipitins) vs. cellular mediated disease (lymphocytic cell infiltration and granuloma formation in lungs)
A number of diagnostic criteria recommendations for HP have been published but none of these sets of criteria have been validated
Investigator---
Major criteria
Minor criteria
Cormier
1. Appropriate exposure
2. Inspiratory crackles
3. Lymphocytic alveolitis (if BAL is done)
4. Dyspnoea
5. Infiltrates on chest radiographs (or HRCT)
1. Recurrent febrile episodes
2. Decreased DLCO
3. Precipitating antibodies to HP antigens
4. Granulomas on lung biopsy (usually not required)
5. Improvement with contact avoidance or appropriate treatment
Schuyler
1. Symptoms compatible with HP
2. Evidence of exposure to appropriate antigen by history or detection in serum and/or BAL fluid antibody
3. Findings compatible with HP on chest radiograph or HRCT
4. BAL fluid lymphocytosis
5. Pulmonary histological changes compatible with HP
6. Positive "natural challenge"
1. Bibasilar rales
2. Decreased DLCO
3. Arterial hypoxaemia, either at rest or during exercise
Terho
1. Exposure to offending antigens (revealed by history aerobiological or microbiologic investigations of the environment, or measurements of antigen-specific IgG antibodies
2. Symptoms compatible with HP present and appearing or worsening some hours after antigen exposure
3. Lung infiltrations compatible with HP visible on chest X-ray
1. Basal crepitant rales
2. Impairment of the diffusing capacity
3. Oxygen tension (or saturation) of the arterial blood either decreased at rest, or normal at rest but decreased during exercise
4. Restrictive ventilation defect in the spirometry
5. Histological changes compatible with HP
6. Positive provocation test whether by work exposure or by controlled inhalation challenge
Richerson
1. The history and physical findings and pulmonary function tests indicate an interstitial lung disease
2. The X-ray film is consistent
3. There is exposure to a recognized cause
4. There is antibody to that antigen
Testing
Specific IgG Antibodies
May be useful as supportive evidence; positive serum antibodies is a significant predictor of HP (odds ratio 5)
Not always identifiable in patients with HP, probably signifying that some antigens causing HP are still unknown
False-negative results may be seen in acute and chronic HP cases
Majority of individuals exposed to an HP antigen develop a high titer of serum precipitating antibodies to the antigen but only 1–15% develop the disease
For example, 10% develop antibodies to farmer's lung antigen Saccharopolyspora rectivirgula but 0.3% develop disease.
The antigens to be tested needs to be determined locally according to the prevalent antigens and patient's history
HP Panel Serology (IBT labs Fluorescence Enzyme Immunoassay; Units Reported: mcg/mL of specific IgG)
Micropolyspora faeni IgG
Thermoactinomyces vulgaris IgG
Aspergillus fumigatus IgG
Penicillium Chrysogenum/notatum IgG
Alternaria tenuis/alternata IgG
Tricoderma viride IgG
Aureobasidium pullulans IgG
Phoma betae IgG
CT Scan
Chest X-ray may be normal in 10%
CT patterns are not specific for HP but HP may be considered in the differential diagnosis when these patterns are present.
Ground-glass opacities can be seen desquamative interstitial pneumonitis, PCP pneumonia, BOOP, bronchoalveolar carcinoma, alveolar proteinosis and alveolar haemorrhage.
When ground-glass opacities are associated with poorly defined, centrilobular micronodules and mosaic attenuation or expiratory air trapping, the diagnosis of HP is further supported
Bronchoalveolar Lavage
Can provide support for diagnosis of HP.
A normal number of lymphocytes rules out all but residual disease. An increase in the total cell count with a remarkable elevation in the percentage of T lymphocytes (often >50%) characterizes HP.
Elevated lymphocytes does notdefinitively establish the diagnosis
Asymptomatic, exposed individuals can have increased BAL lymphocytes (due to normal inflammatory response or mild self-limited alveolitis)
Many other diseases (sarcoidosis, interstitial pneumonia associated with collagen vascular disease, silicosis, BOOP, HIV pneumonitis and drug-induced pneumonitis) are characterized by an alveolar lymphocytosis
Increased lymphocytes in a patient with interstitial lung disease of unknown origin should direct the clinician towards the possible diagnosis of HP
A predominance of CD8+ T cells and a CD4+/ CD8+ ratio lower than 1 is often (but notalways) observed in HP whereas a high CD4+/CD8+ ratio is associated with sarcoidosis (CD4/CD8 ratio >4 has 100% positive predictive value for sarcoidosis).
Exceptions:
CD4/CD8 ratio can be increased in HP to levels as high as those seen in sarcoidosis
Low CD4+/CD8+ ratio may be associated with chronic HP and to asymptomatic individuals with HP whereas a predominance of CD4+ T cells is related to the acute phase of the disease.
CD4+/CD8+ ratio may depend on the type/amount/duration of antigen exposure.
Overall, the evaluation of CD4+ and CD8+ T cell subsets is not recommended for clinical practice, because a growing body of evidence has shown that these subsets and their ratio diverge according to a number of situations, including the type of inhaled antigen, the intensity of exposure, smoking, and the clinical stage
PFTs
Typical physiological profile of acute HP is a restrictive pattern with low DLCO
Decreased DLCO is not always present in HP (in one study, up to 22% with HP had normal DLCO)
HP Diagnostic Algorithm
Treatment
Avoidance of the offending antigen
Corticosteroid
Help control symptoms of acute or subacute disease but do not seem to affect the long-term outcome
The dose of corticosteroids to be given is unclear and based on expert opinion
Most recommend 50 mg of oral prednisone daily; others suggest that 20 mg would be sufficient
2-4 weeks of prednisone 0.5 mg/kg/day may be appropriate in acute phase; subacute HP might require higher doses for several months
Clinical Features
Table of Contents
Causative Antigens and Sources
Farming
Ventilation and water-related contamination
Birds and poultry handling
Veterinary work and animal handling
Grain and flour processing
Milling and construction
Plastic manufacturing, painting, electronics industry, and other chemicals
Textile workers
Differential Diagnosis
Note:
Diagnosis
Predictors of HP
Diagnostic Criteria
2. Inspiratory crackles
3. Lymphocytic alveolitis (if BAL is done)
4. Dyspnoea
5. Infiltrates on chest radiographs (or HRCT)
2. Decreased DLCO
3. Precipitating antibodies to HP antigens
4. Granulomas on lung biopsy (usually not required)
5. Improvement with contact avoidance or appropriate treatment
2. Evidence of exposure to appropriate antigen by history or detection in serum and/or BAL fluid antibody
3. Findings compatible with HP on chest radiograph or HRCT
4. BAL fluid lymphocytosis
5. Pulmonary histological changes compatible with HP
6. Positive "natural challenge"
2. Decreased DLCO
3. Arterial hypoxaemia, either at rest or during exercise
2. Symptoms compatible with HP present and appearing or worsening some hours after antigen exposure
3. Lung infiltrations compatible with HP visible on chest X-ray
2. Impairment of the diffusing capacity
3. Oxygen tension (or saturation) of the arterial blood either decreased at rest, or normal at rest but decreased during exercise
4. Restrictive ventilation defect in the spirometry
5. Histological changes compatible with HP
6. Positive provocation test whether by work exposure or by controlled inhalation challenge
2. The X-ray film is consistent
3. There is exposure to a recognized cause
4. There is antibody to that antigen
Testing
Specific IgG Antibodies
Hypersensitivity Pneumonitis Panel by Precipitin
Johns Hopkins DACI Reference Lab - Precipitins
HP Panel Serology (IBT labs Fluorescence Enzyme Immunoassay; Units Reported: mcg/mL of specific IgG)
CT Scan
Bronchoalveolar Lavage
PFTs
HP Diagnostic Algorithm
Treatment
References